Functional MRI, drugs, and poststroke recovery.

Stroke is the first cause of disability in industrialized countries. Thus, understanding the mechanisms of poststroke recovery appears to be crucial in improving motor performance and reducing disability in stroke patients. Strategies through which brain restores lost functions after ischemic lesions are numerous. The mechanisms underlying poststroke recovery, known as cerebral plasticity, are so far hypothetical. However, functional magnetic resonance imaging (fMRI) studies recently have provided new insights in to stroke recovery. This article sketches out the mechanisms that are thought to underly recovery and focuses on fMRI experimental studies that have investigated the influence of a number of drugs on functional recovery. Functional MRI is a valuable tool in understanding functional recovery and may help to disclose new therapeutical approaches.

Chronic administration of selective serotonin reuptake inhibitor (SSRI) paroxetine modulates human motor cortex excitability in healthy subjects.

The aim of the study was to investigate the effect of chronic administration of paroxetine (selective serotonin reuptake inhibitor: SSRI) on motor cortex excitability in healthy subjects by means of transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI) and behavioral motor tests. In a randomized, double-blind, crossover study, twenty-one right-handed subjects received 20 mg daily of either paroxetine or a placebo over a period of 30 days separated by a period of 3 months wash-out. The TMS study is presented here correlated with some results of the motor behavior study (finger tapping test) and the fMRI study (primary sensorimotor cortex (S1M1) volume of activation). TMS was used to test motor threshold (MT), motor evoked potential recruitment curve (RC), cortical silent period (CSP) and paired-pulse intracortical inhibition and facilitation (ICI, ICF). Chronic administration of paroxetine did not modulate ICI or CSP but induced a significant enhancement of mean ICF (ANOVA P=0.04), which significantly correlated with increase of speed in a finger tapping test (P=0.02). This suggests a modulation of cortical interneuronal excitatory pathways without changes in the excitability of cortical inhibitory GABAergic interneurons. A decrease of RC (ANOVA P=0.05) was also observed after 30 days intake of paroxetine in comparison with placebo and was associated with changes of fMRI activation intensity (left S1M1 hypoactivation, ), without changes of S1M1 activation volume. Finally, the different modulation of RC and ICF after chronic administration of paroxetine compared to single dose (opposite effects) emphasizes the different pharmacological action of the drug at cortical level depending on its acute or long-term administration.

Diazepam effects on the cerebral responses to tonic pain: a SPET study.

RATIONALE: Pain is a complex phenomenon with a strong affective-emotional component in addition to a sensory-discriminative one. This causes the activation of multiple brain areas, which process different aspects of pain simultaneously. OBJECTIVES: We investigated the effects of diazepam (DZ) on a well-known pattern of brain regions activated by cold, tonic pain stimuli. METHODS: Quantitative cerebral blood flow (CBF) was assessed by single photon emission tomography (SPET) and the Xe-133 inhalatory method, at rest and during tonic pain activation in eight normal, right-handed, male volunteers. The cold pressor test (CPT) was performed by immersion of the left hand in cold water twice, first during CPT alone, and again 30 min after intravenous administration of diazepam (CPT+DZ). RESULTS: During CPT we observed a significant CBF increase in the right thalamus, primary sensory-motor cortex (S1/M1), frontal and temporal regions, and in the left temporal region and anterior cingulate cortex (ACC). During CPT+DZ, the average CBF was significantly lower than during the CPT state (-11%, P<0.05). After normalisation, during CPT+DZ we again observed a significant CBF increase in the right thalamus, S1/M1 and frontal regions, and in the left ACC, though not in the temporal regions. DZ administration first causes a global reduction in CBF, then modifies the pattern of brain activation. CONCLUSIONS: During CPT, activation of the temporal regions has been interpreted as part of the affective-emotional component of pain response. DZ seems to affect the "pain-related" pattern of activation by abolishing the CBF increase in the temporal regions, without, however, modifying the pain perception or determining a sedating effect.

Usefulness of primitive reflexes in demented and non-demented cerebrovascular patients in daily clinical practice.

The aim of this study was to investigate the usefulness of primitive reflexes (PRs) as additional alert signs in a routine clinical setting of cognitive decline in an elderly population of chronic ischemic cerebrovascular patients. We considered the occurrence of grasp, palmomental, glabellar and snout reflexes in 75 demented (VaD) and 75 non-demented (VaND) patients, and in 75 healthy elderly controls. We never elicited more than two PRs in controls. The occurrence of three or four PRs provided the strongest correlation with dementia (p < 0.0001), with 93% specificity irrespective of low sensitivity. In conclusion, the occurrence of more than two PRs might serve as an additional warning sign of possible mild cognitive impairment in chronic ischemic cerebrovascular patients.

Tonic pain: a SPET study in normal subjects and cluster headache patients.

Whether the pathogenesis of cluster headache (CH) is peripheral or central is still matter of debate. An involvement of central structures related to pain perception and modulation, which also causes an alteration of the physiological pattern of pain perception in CH, has been hypothesized. We investigated the pattern of brain response to pain in normal subjects and CH patients by evaluating the cerebral blood flow (CBF) changes using an experimental model of tonic aching pain stimulation, the cold water pressor test (CWPT). CBF was assessed quantitatively by the Xe-133 inhalation method and single photon emission tomography (SPET), at rest and during CWPT, as previously described (Di Piero et al., 1994). CWPT was performed in 12 volunteers and in seven patients with CH. All the CH patients had a left-sided headache and were studied in a headache-free phase out of the cluster period. During CWPT, volunteers showed a significant CBF increase in the contralateral primary sensorimotor (P < 0.001), frontal (P < 0.01) and temporal (P < 0.002) regions and thalamus (P < 0.01) and in the ipsilateral temporal (P < 0.005) and anterior cingulate (P < 0.01) regions. During left-hand stimulation (ipsilateral to the headache side) by CWPT in CH patients, CBF changes were significantly lower than those observed in volunteers in the contralateral primary sensorimotor region (P < 0.0005) and thalamus region (P < 0.01). There were no significant differences in the brain response observed during the stimulation of the hand contralateral to the headache side. In conclusion, in a headache-free phase out of the cluster period, the pattern of cerebral activation during tonic pain stimulation of the hand ipsilateral to the headache side is critically modified in CH patients in areas which are probably involved in the detection of the stimulus intensity. This modification may reflect a marker of a biological modification of the pain conveyance system. The fact that it is also present out of the active period of the disease, suggests a possible involvement of central tonic pain mechanisms in the pathogenesis of CH.